ANTIBODIES AS TOOLS IN CARDIOVASCULAR RESEARCH

抗体作为心血管研究的工具

• 批准号: 3097727
• 负责人: EDGAR HABER
• 金额: $ 121.23万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-06-01 至 1986-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3097727
• 关键词: drug adverse effect; drug metabolism; heart pharmacology; monoclonal antibody

The evolution of our understanding of the structure and function of the antibody combining site has advanced to the point that one can now realistically contemplate the application of antibodies as reagents or drugs of remarkable specificity. Unlike the conventional drug, which is a small organic molecule that allows a limited number of contacts with its target site, the antibody combining site is relatively capacious. This permits numerous interatomic contacts with a ligand, allowing for remarkable selectivity as well as very high affinity. The development of cell fusion methods for producing antibodies now permits the production of homogeneous antibodies of defined specificity in a reproducible manner. In the proposed program, the antibody combining site will be investigated as a major tool in cardiovascular research. On a most basic level, the combining site of antibodies specific for digoxin will be dissected with respect to its primary structure so that antibodies suitable for therapeutic use might be produced by chemical synthesis or alternatively by translation a gene message. Again utilizing digoxin specific antibody as a model, antibody fragments will be examined with respect to their pharmacologic properties in clinical studies. The resolution of molecular properties allowed by the specificity of the antibody combining site will be utilized to advantage in the dissection of the physiology, pathophysiology, and biosynthesis of renin; in the understanding of the properties and purification of adrenergic receptor antibodies; and in the elucidation of the function of prostaglandin and angiotensin receptors. The investigators in all these projects have as a common research tool the antibody combining site and utilize conjointly the facilities of a protein chemistry and cell fusion laboratory to produce and understand the reagents that they utilize.

我们对抗体结构和功能认识的进化